Research Design and Methods Ten glucose-tolerant offspring of patients with NIDDM and 10 age-, sex-, and weight-matched healthy control subjects without family history of diabetes were studied with the minimal model method of Bergman et al. Body fat composition and distribution pattern were assessed by the bioelectrical impedance analyzer and waist-hip circumference ratios (WHR), respectively, in each subject.

Results Mean fasting serum glucose (4.39 ± 0.17 vs. 3.94 ± 0.17 mM) and postglucose peak (18.50 ± 1.50 vs. 13.20 ± 1.06 mM) levels were significantly greater (P < 0.05) in the offspring than in the control subjects. Mean fasting serum insulin levels were slightly greater but not significantly different in the offspring versus control subjects (64 ± 14 vs. 29 ± 7 pM). After intravenous stimulation with glucose and tolbutamide, the mean serum insulin rose to significantly greater (P < 0.05) levels at t = 5 and 25 min in the offspring compared with the control subjects. Mean SI was significantly reduced by 45% in the offspring compared with the control subjects (4.77 ± 0.67 vs. 8.37 ± 1.24 × 10-4 min−1 · mU-1 · L-1;). However, SG was not different in the offspring versus control subjects (1.92 ± 0.12 vs. 2.10 ± 0.17 × 10-2 min−1). SI correlated significantly and inversely with the percentage of body fat mass (r = −0.580, P < 0.05) but not with the WHR (r = −0.019) in the offspring. We found a negative association between SI and basal serum insulin (r = −0.798, P < 0.01) but not with the poststimulation incremental insulin responses in the offspring. Family history of diabetes independently accounted for at least 27% of variance in the SI in our subjects.

Conclusions Our study confirmed that insulin insensitivity but not a reduced glucose effectiveness exists in young glucose-tolerant offspring of patients with NIDDM. The reduced SI appears to be causally related to the total body fat content and may be a familial and/or genetic trait in the offspring.